Differential effects of pro‐BDNF on sensory neurons after sciatic nerve transection in neonatal rats

Fan, Ying; Wu, Linda Lin-yan; Liu, Hongyun; Wang, Yan‐Jiang; Zhou, Xin‐Fu

doi:10.1111/j.1460-9568.2008.06215.x

Cited by 49 publications

(41 citation statements)

References 61 publications

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“…As this anti-proBDNF antibody can neutralize the biological activities of proBDNF in neurons (Fan et al, 2008;Sun et al, 2012;Xu et al, 2011), we wished to establish whether anti-proBDNF treatment can reverse the behavioral and pathological impairments in rats caused by chronic stress. The present study showed that i.c.v.…”

Section: Discussionmentioning

confidence: 99%

“…injected with one single dose of sheep anti-proBDNF (Fan et al, 2008;Lim et al, 2015) antibody (10 μg,1 μg/μl) on day 22 with a Hamilton syringe, and then behaviorally assessed on days 23, 24, and 25 ( Figure 3a); (2) i.p. injected with one dose of anti-proBDNF antibody (10 μl, 0.08 μg/μl per g of body weight) on day 22, followed by one half the dose on day 26, and behaviorally assessed on days 27, 28, and 29 ( Figure 3a); and (3) i.m.…”

Section: Animal Surgery and Microinjectionmentioning

confidence: 99%

“…Western blot, RT-PCR, ELISA, and immunostaining were performed as previously described (Fan et al, 2008;Lim et al, 2015;Yang et al, 2014), and detailed procedures are described in Supplementary Material.…”

Section: Mrna and Protein Detectionsmentioning

confidence: 99%

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ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Bai

Ruan

Yang

et al. 2016

Neuropsychopharmacol

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104

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Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific antiproBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Animal Surgery and Microinjectionmentioning

confidence: 99%

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ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Bai

Ruan

Yang

et al. 2016

Neuropsychopharmacol

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104

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“…ProBDNF is synthesized and subsequently cleaved, either intracellularly, by prohormone convertases and furin, or extracellularly, by plasmin and matrix metalloproteinases (MMPs), to generate mature BDNF (6,7). Mature BDNF and proBDNF exert opposing effects through two different transmembrane receptor signaling systems, consisting of tyrosine receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) to modulate cell apoptosis (8)(9)(10), long-term depression (11) and synaptic plasticity (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

et al. 2015

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Abstract. There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.

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“…Their diverse actions are mediated through two different transmembrane receptor signalling systems: Trk tyrosine kinase B (TrkB) receptor and p75 neurotrophin receptor (NTR). Mature BDNF activates the high affinity TrkB receptor, promoting cell survival while proBDNF binds to both p75NTR and the co-receptor sortilin with a high affinity, to modulate cell apoptosis (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Mature BDNF promotes the growth of glioma cells in vitro

et al. 2013

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Abstract. High-grade glioma is incurable and is associated with a short survival time and a poor prognosis. There are two forms of brain-derived neurotrophic factor (BDNF), proBDNF and mature BDNF, which exert opposite effects. Their diverse actions are mediated through two different transmembrane receptor signalling systems: p75NTR and TrkB. The important roles of the BDNF/TrkB signalling system in tumour cell proliferation and survival have been demonstrated. However, few studies have been able to distinguish mature BDNF from proBDNF due to the limitation of specific antibodies. Using specific proBDNF antibodies, we demonstrated that the proBDNF/p75NTR pathway appears to inhibit malignant glioma cell growth and migration. In the present study using specific mature BDNF antibodies, we found that mature BDNF inhibited C6 glioma cell apoptosis and increased cell growth and migration in vitro. Our data suggest that the counterbalance between mature BDNF and proBDNF may regulate tumour growth. IntroductionBrain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is known to regulate cell growth, differentiation, migration and apoptosis in the nervous system (1,2). There are two forms of BDNF, a precursor and a mature form, in the central nervous system (CNS) (3). The precursor of BDNF (proBDNF) is synthesised and subsequently cleaved either intracellularly by prohormone convertases (PCs) and/ or furin, or extracellularly by plasmin and matrix metalloproteases (MMPs) to release the mature homodimeric protein (mature BDNF) (4,5). Their diverse actions are mediated through two different transmembrane receptor signalling systems: Trk tyrosine kinase B (TrkB) receptor and p75 neurotrophin receptor (NTR). Mature BDNF activates the high affinity TrkB receptor, promoting cell survival while proBDNF binds to both p75NTR and the co-receptor sortilin with a high affinity, to modulate cell apoptosis (6-8).Increasing evidence suggests that altered signalling through TrkB promotes tumour formation and metastasis. TrkB, in conjunction with its primary ligand BDNF, is often overexpressed in a variety of human cancers, ranging from neuroblastomas to pancreatic ductal adenocarcinomas, where it may allow tumour expansion and contribute to resistance to antitumour agents (9). Neurotrophin genes were found to be expressed in 24 cell lines derived from human malignant gliomas, and the BDNF gene was most abundantly expressed (10). Expression of Trk receptors (TrkA, TrkB and TrkC) has been detected in human astrocytomas and promotes tumour growth. Furthermore, activation of the JNK pathway may contribute to progression towards malignancy (11). Expression of BDNF and TrkB is also observed in human gangliogliomas (12). However, histological data in previous studies were unable to distinguish mature BDNF from proBDNF due to the lack of specific antibodies. We generated specific antibodies to mature BDNF and proBDNF, respectively. In our recent study, the proBDNF/p75NTR pathway appeared to inhibit malignant glioma cell gr...

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Differential effects of pro‐BDNF on sensory neurons after sciatic nerve transection in neonatal rats

Cited by 49 publications

References 61 publications

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Mature BDNF promotes the growth of glioma cells in vitro

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